X-Ray Absorption from the Milky Way Halo and the Local Group

Million degree gas is present at near-zero redshift and is due either to a gaseous Galactic Halo or a more diffuse but very massive Local Group medium. We can discriminate between these models because the column densities should depend on location in the sky, either relative to the Galaxy bulge or to the M31-Milky Way axis. To search for these signatures, we measured the OVII Kalpha absorption line strength toward 25 bright AGNs, plus LMC X-3, using XMM-Newton RGS archival data. The data are in conflict with a purely Local Group model, but support the Galactic Halo model. The strongest correlation is between the OVII equivalent widths and the ROSAT background emission measurement in the R45 band (0.4-1 keV), for which OVII emission makes the largest single contribution. This suggests that much of the OVII emission and absorption are cospatial, from which the radius of a uniform halo appears to lie the range 15-110 kpc. The present data do not constrain the type of halo gas model and an equally good fit is obtained in a model where the gas density decreases as a power-law, such as r^(-3/2). For a uniform halo with a radius of 20 kpc, the electron density would be 9E-4 cm^(-3), and the gas mass is 4E8 Msolar. The redshift of the four highest S/N OVII measurements is consistent with a Milky Way origin rather than a Local Group origin.Comment: 32 pages (14 figures); ApJ, in pres

On the Lack of a Soft X-Ray Excess from Clusters of Galaxies

A soft X-ray excess has been claimed to exist in and around a number of galaxy clusters and this emission has been attributed to the warm-hot intergalactic medium that may constitute most of the baryons in the local universe. We have re-examined a study of the XMM-Newton observations on this topic by Kaastra et al. (2003) and find that the X-ray excess (or deficit) depends upon Galactic latitude and appears to be most closely related to the surface brightness of the 1/4 keV emission, which is largely due to emission from the Local hot bubble and the halo of the Milky Way. We suggest that the presence of the soft X-ray excess is due to incorrect subtraction of the soft X-ray background. An analysis is performed where we choose a 1/4 keV background that is similar to the background near the cluster (and for similar HI column). We find that the soft X-ray excess largely disappears using our background subtraction and conclude that these soft X-ray excesses are not associated with the target clusters. We also show that the detections of "redshifted" O VII lines claimed by Kaastra et al. (2003) are correlated with solar system charge exchange emission suggesting that they are not extragalactic either.Comment: 8 pages, 6 figures, accepted for publication in Ap

Robustness of adiabatic quantum computation

We study the fault tolerance of quantum computation by adiabatic evolution, a quantum algorithm for solving various combinatorial search problems. We describe an inherent robustness of adiabatic computation against two kinds of errors, unitary control errors and decoherence, and we study this robustness using numerical simulations of the algorithm.Comment: 11 pages, 5 figures, REVTe

Elemental Abundances in the X-Ray Gas of Early-Type Galaxies with XMM and Chandra Observations

The source of hot gas in elliptical galaxies is thought to be due to stellar mass loss, with contributions from supernova events and possibly from infall from a surrounding environment. This picture predicts supersolar values for the metallicity of the gas toward the inner part of the galaxy, which can be tested by measuring the gas phase abundances. We use high-quality data for 10 nearby early-type galaxy from XMM-Newton, featuring both the EPIC and the Reflection Grating Spectrometer, where the strongest emission lines are detected with little blending; some Chandra data are also used. We find excellent consistency in the elemental abundances between the different XMM instruments and good consistency with Chandra. Differences in abundances with aperture size and model complexity are examined, but large differences rarely occur. For a two-temperature thermal model plus a point source contribution, the median Fe and O abundances are 0.86 and 0.44 of the Solar value, while Si and Mg abundances are similar to that for Fe. This is similar to stellar abundances for these galaxies but supernovae were expected to enhance the gas phase abundances considerably, which is not observed.Comment: 35 pages, 10 figures, accepted for publication in Astrophysical Journa

X-Ray Searches for Emission from the WHIM in the Galactic Halo and the Intergalactic Medium

At least 50% of the baryons in the local universe are undetected and predicted to be in a hot dilute phase (1E5-1E7 K) in low and moderate overdensity environments. We searched for the predicted diffuse faint emission through shadowing observations whereby cool foreground gas absorbs more distant diffuse emission. Observations were obtained with Chandra and XMM-Newton. Using the cold gas in two galaxies, NGC 891 and NGC 5907, shadows were not detected and a newer observation of NGC 891 fails to confirm a previously reported X-ray shadow. Our upper limits lie above model predictions. For Local Group studies, we used a cloud in the Magellanic Stream and a compact high velocity cloud to search for a shadow. Instead of a shadow, the X-ray emission was brighter towards the Magellanic Stream cloud and there is a less significant brightness enhancement toward the other cloud also. The brightness enhancement toward the Magellanic Stream cloud is probably due to an interaction with a hot ambient medium that surrounds the Milky Way. We suggest that this interaction drives a shock into the cloud, heating the gas to X-ray emitting temperatures.Comment: 10 ApJ pages with 10 figure

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care